Summary

UCLA researchers have discovered a new population of adult stem cells and a method of their isolation that demonstrate advantages over embryonic and induced pluripotent stem cells for regenerative medicine applications.

Background

Pluripotent stem cells (PSCs) are distinguished by their ability to proliferate indefinitely and differentiate into any cell type. Owing to these characteristics, PSCs represent a theoretically potent source of human tissue for regenerative medicine. Some prospective applications include growing organs in vitro for transplantation, repairing heart muscle damaged by ischemia or disease, and curing diabetes by implanting cultured pancreatic beta cells.

There are currently two main sources of PSCs. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC). ESCs can be isolated from early stage embryos, though their use is fraught with ethical controversy. Reprogramming adult somatic cells to produce iPSC circumvents moral issues, but is still in its infancy. Unfortunately, both ECS and iPSCs exhibit an uncontrolled in vivo capacity for differentiation and proliferation, leading to the risk of unwanted teratoma formation in transplant recipients. Despite many efforts in the study of both PSCs, there has been little progress made in resolving the defects that stand in the way of their use in cell therapies for humans. Only two clinical trials have thus been implemented, one by Dr. Robert Lanza and his research team at the University of California, Los Angeles, and the other by the biopharmaceutical company, Geron, the latter of the two halting its clinical trial in 2011.

There is thus a need to identify a new population of human pluripotent stem cells; one that not only differentiates into other cell types, but also, one that does not produce potentially-malignant teratomas.

Innovation

Researchers at the UCLA School of Medicine have recently discovered a new population of human pluripotent adult stem cells (pluripotent adipose stem cells, PASCs) isolated from lipoaspirate material by using a novel methodology, without the need of extrinsically-induced differentiation genes, and without further need of multiple purification steps (e.g. cell sorting, magnetic beads, etc). Similar to ESCs and iPSC, PASCs grow in suspension forming cell spheres, express the classical the pluripotent stem cell markers (SSEA3, Nanog, Oct3/4, SOX2 and Kfl4), express a variety of markers of all three germlines, and upon culture in differentiation mediums, express the full differentiation capacity into endodermal, ectodermal and messodermal cell lineages. In contrast to ESCs and iPSC, PASCs do not form teratomas in mammalian animal models. Lipoaspirate material used a source of PASCs is obtained by a non-invasive procedure requiring only local anesthesia. PASCs can be isolated using a simple technique without the need of cell sorting, magnetic beads, and long term cell culture procedures. PASCs can be easily isolated by an adequately-trained medical technician. PASCs isolated from human adipose tissue open an entirely new avenue in the field of regenerative medicine and cell therapy.

Applications

Generation of patient-derived tissue for transplantation

Source of cells at various developmental stages for research, including drug screening

PASCs can be isolated using a simple purification step without the need of further purification steps (e.g. cell sorting, magnetic beads, etc).

PASC isolation require minimum cell manipulation.

PASCs yield pluripotent stem cells after few days, in contrast to the weeks associated with generating ESC and iPSCs.

PASCs do not form teratomas in animal models.

State Of Development

The inventors have developed methods of isolating and characterizing PASCs from human adipose tissue. After demonstrating that PASCs can be recognized by the pluripotent stem cell markers (SSEA3, Nanog, Oct3/4, SOX2 and Kfl4), express a variety of markers of all three germlines, and upon culture in differentiation mediums, express the full differentiation capacity into endodermal, ectodermal and messodermal cell lineages, the researchers are now employing to determine the precise role of PASCs in human health and disease. Planning is currently underway for tissue regeneration studies in different animal models.